Plasma Metabolite Profiles of Alzheimer’s Disease and Mild Cognitive Impairment

• Published in: Journal of proteome research Vol. 13; no. 5; pp. 2649 - 2658
• Main Authors: Wang, Gang, Zhou, Yi, Huang, Feng-Jie, Tang, Hui-Dong, Xu, Xu-Hua, Liu, Jia-Jian, Wang, Ying, Deng, Yu-Lei, Ren, Ru-Jing, Xu, Wei, Ma, Jian-Fang, Zhang, Yi-Nan, Zhao, Ai-Hua, Chen, Sheng-Di, Jia, Wei
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 02.05.2014
• Subjects: Aged; Aged, 80 and over; Alzheimer disease; Alzheimer Disease - blood; Alzheimer Disease - diagnosis; Alzheimer Disease - metabolism; amino acid metabolism; arachidonic acid; Arachidonic Acid - blood; biomarkers; Biomarkers - blood; Biomarkers - metabolism; Chromatography, Liquid; Cognitive Dysfunction - blood; Cognitive Dysfunction - diagnosis; Cognitive Dysfunction - metabolism; cytidine; Cytidine - blood; drug therapy; early diagnosis; fatty acid metabolism; Gas Chromatography-Mass Spectrometry; glutamic acid; Glutamic Acid - blood; glutamine; Glutamine - blood; Humans; liquids; Male; Mass Spectrometry; metabolites; Metabolomics - methods; Middle Aged; nucleic acids; patients; proteome; Reproducibility of Results; Sarcosine - analogs & derivatives; Sarcosine - blood; Sensitivity and Specificity; thymine; Thymine - blood; Alzheimer’s disease; amnestic mild cognitive impairment; plasma; metabolomics; biomarkers
• ISSN: 1535-3893; 1535-3907; 1535-3907
• DOI: 10.1021/pr5000895

Previous studies have demonstrated altered metabolites in samples of Alzheimer’s disease (AD) patients. However, the sample size from many of them is relatively small and the metabolites are relatively limited. Here we applied a comprehensive platform using ultraperformance liquid chromatography-time-of-flight mass spectrometry and gas chromatography-time-of-flight mass spectrometry to analyze plasma samples from AD patients, amnestic mild cognitive impairment (aMCI) patients, and normal controls. A biomarker panel consisting of six plasma metabolites (arachidonic acid, N,N-dimethylglycine, thymine, glutamine, glutamic acid, and cytidine) was identified to discriminate AD patients from normal control. Another panel of five plasma metabolites (thymine, arachidonic acid, 2-aminoadipic acid, N,N-dimethylglycine, and 5,8-tetradecadienoic acid) was able to differentiate aMCI patients from control subjects. Both biomarker panels had good agreements with clinical diagnosis. The 2 panels of metabolite markers were all involved in fatty acid metabolism, one-carbon metabolism, amino acid metabolism, and nucleic acid metabolism. Additionally, no altered metabolites were found among the patients at different stages, as well as among those on anticholinesterase medication and those without anticholinesterase medication. These findings provide a comprehensive global plasma metabolite profiling and may contribute to making early diagnosis as well as understanding the pathogenic mechanism of AD and aMCI.